Cardiovascular disease is the greatest cause of morbidity and mortality in the industrialized world. It not only strikes down a significant fraction of the population without warning but also causes prolonged suffering and disability in an even larger number.
Atrial fibrillation (AF) is a common arrhythmia, affecting approximately 1% of the general population and 8% of those over the age of 80. As a result, AF places a substantial financial burden on the healthcare system, accounting for over $6 billion in direct treatment costs in the United States in 2006. More importantly, AF is associated with substantial morbidity and mortality. For example, several studies have documented a two-fold increase in mortality and a 2 to 7-fold increase in stroke rate for patients in AF compared to age-matched controls in normal sinus rhythm. Unfortunately, current pharmacologic therapy for the prevention of AF (anti-arrhythmic drugs) is hampered by major dose-limiting toxicities and high rates of arrhythmia recurrence.
In some cases, radio-frequency catheter ablation of the pulmonary veins is used to isolate unorganized electrical activity generated therein to prevent AF. Current catheter based techniques generally use an anatomic approach to identify ablation targets—regions targeted for radio-frequency ablation are identified largely based on their anatomic proximity to the pulmonary veins resulting in the same basic set of ablation lesions being generated in all patients. Using this approach, however, long-term success has been limited with an AF recurrence rate of up to 50% within 12 months following a single ablation procedure. The limited efficacy of pulmonary vein ablation is at least partly due to the fact that atrial fibrillation is a heterogeneous disease and arises from different sites in different patients.
In fact, many non-pulmonary vein sites have been identified as potential triggers for AF. Unfortunately, methods to identify these other sites during ablation procedures are lacking. In addition to the pulmonary veins, other cardiac veins are potentially arrhythmogenic, and may also be involved in the initiation and perpetuation of AF.
More recent techniques for AF ablation have used complex electroanatomic mapping systems to identify non-pulmonary vein sites as targets for ablation. These newer methods are technically complex, difficult to apply broadly and still do not provide an easily applied measure for defining the adequacy of ablation.
Pulmonary vein ablation is hampered by safety concerns with a major complication rate around 6%, including stroke, pulmonary vein stenosis, cardiac tamponade, atrio-esophageal fistula and death. In most cases, complications of catheter ablation occur as a result of thermal injury to the atrium and surrounding structures. Limiting the amount of tissue targeted for ablation may prevent complications from thermal injury but may also compromise efficacy by leaving behind un-ablated sites that later serve as the substrate for recurrent AF. One of the major limitations of the anatomic approach to pulmonary vein ablation has been the inability to determine, in real-time, when enough tissue has been ablated to achieve a successful outcome—that is no recurrence of AF.